Through this application Baylor College of Medicine seeks to renew funding for P50-58201, Specialized Program of Research Excellence (SPORE) in Prostate Cancer. Under the leadership of investigators recognized internationally for their research in prostate cancer and with the support provided by the SPORE, Baylor has created a solid infrastructure for prostate cancer research that provides creative investigators with the resources to move ideas rapidly from the laboratory to the clinic with t he goal of reducing the incidence, morbidity and mortality from prostate cancer. In our initial application the research was directed toward the early stages of the disease, on markers of progression, new animal models and chemoprevention as a novel intervention strategy. Reflecting progress in our SPORE and other centers, we have modified our strategy substantially to develop a systematic plan of 5 well defined Translational Research Objectives designed to expand the narrow window of opportunity for successful intervention against prostate cancer: 1) new markers of progression and metastasis that accurately reflect the threat posed by the cancer; 2) novel methods for low-risk definitive therapy of early stage cancer, induction of cell death through gene therapy or growth inhibition and differentiation induction through biological modifiers); 3) chemoprevention with biologic agents such as retinoids or vitamin D analogs; 4) novel strategies for adjuvant therapy (biologic agents to suppress metastases after surgery, and gene therapy as a radiation enhancer or with cytokines to suppress metastasis after surgery); and 5) treatment for advanced disease with biologic agents. Progress toward these objectives will be assured by small, efficient, highly interactive, multidisciplinary teams of senior basic scientists and clinical investigators organized into 5 Translational Steering Groups (TSGs): clinical markers; gene therapy and molecular genetics; transgenic animal models; biological therapy; and mesenchymal regulation of prostate growth. This mechanism will allow the scientific disorders of a the SPORE (the P.I. and Scientific Coordinator) to monitor progress closely and assure continual focus on the translational research objectives of the SPORE. The 7 research projects included will continue our previous investigations of clinical marker, biological therapy, and transgenic model systems. Novel additions include projects addressing cell cycle regulation of prostate cancer growth, mesenchymal regulation of prostate cancer growth and gene therapy for prostate cancer-supported by 4 core facilities specific projects and cores. With a very large and multiethnic patient population and considerable institutional resources committed to space, funds and personnel and with a proven multidisciplinary team of investigators. Baylor seeks to continue its studies in prostate cancer through this SPORE to advance the field through specific Translational Research Objectives, which will ultimately provide essential new information and novel therapeutic approaches toward reduction in the incidence and mortality rate from this-devastating disease.